Increased levels of blood platelet-activating factor (PAF) and PAF-like lipids in patients with ischemic stroke

Satoh, Kei; Imaizumi, Tada Atsu; Yoshida, Hidemi; Hiramoto, M.; Takamatsu, Shigeru

doi:10.1111/j.1600-0404.1992.tb04010.x

Cited by 45 publications

(26 citation statements)

References 30 publications

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“…It has been shown earlier that PAF-AH activity in plasma LDL increases in ischemic stroke (18), leading the authors to postulate that the latter might be an adaptation to an increased amount of bioactive PAF-like phospholipids generated upon stroke (21). More recently, Packard et al (19) found, in a prospective nested case-control study, that increased levels of PAF-AH showed a strong positive association with the risk of coronary heart disease in a population of middle-aged men with hypercholesterolemia.…”

Section: Discussionmentioning

confidence: 99%

Plasma PAF-acetylhydrolase in patients with coronary artery disease: results of a cross-sectional analysis

Blankenberg

Stengel

Rupprecht

et al. 2003

Journal of Lipid Research

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Inflammation underlies both onset and perpetuation of atherosclerosis. Plasma lipoproteins transport the platelet-activating factor-acetylhydrolase (PAF-AH) with potentially anti-inflammatory activities. Our aim was to determine whether PAF-AH activity was associated with inflammatory markers and with coronary artery disease (CAD). PAF-AH activity and a panel of inflammatory mediators were measured in plasma of 496 patients with CAD and in 477 controls; 276 patients presented with stable angina pectoris and 220 with acute coronary syndrome (ACS). Individuals within the highest quartile of PAF-AH activity had an 1.8-fold increase in CAD risk [95% confidence interval (CI), 1.01 to 3.2; P ‫؍‬ 0.048] compared with those in the first quartile (adjusted for clinical and metabolic factors). When excluding individuals receiving statin and angiotensin-converting enzyme-inhibitor medication, individuals within the highest quartile of PAF-AH activity revealed a 3.9-fold increase in CAD risk (95% CI, 2.0 to 7.7; P Ͻ 0.0001). In these subjects, the plasma PAF-AH activity increased gradually in stable angina and in ACS both in men ( P Ͻ 0.0001) and in women ( P Ͻ 0.001), as compared with controls. No correlation was found between PAF-AH levels and those of common markers of inflammation. This study and the previous ones raise the important issue of whether PAF-AH is simply a marker of risk or directly promotes atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Plasma PAF-acetylhydrolase in patients with coronary artery disease: results of a cross-sectional analysis

Blankenberg

Stengel

Rupprecht

et al. 2003

Journal of Lipid Research

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“…Indirect evidence supporting the notion that PAF-like lipids have pathological effects includes the fact that a deficiency of PAF-AH is correlated with an increased risk of stroke 30 and increased levels of circulating PAF-like lipids. 31 …”

Section: Pathological Activationmentioning

confidence: 99%

Sol Sherry Lecture in Thrombosis

Prescott

McIntyre

Zimmerman

et al. 2002

ATVB

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Abstract-The inflammatory response is characterized by a multistep molecular interaction between "signaling" cells, such as endothelial cells, and "responding" cells, such as neutrophils and monocytes. In the first step, selectins produced by signaling cells mediate the tethering of responding cells at sites of inflammation. Subsequently, an additional mediator expressed by signaling cells activates the tethered responding cells. Under pathological conditions, the same mechanism is invoked in inappropriate ways: (1) by prolonged presentation of selectins on the cell surface and (2) by the unregulated production of oxidized phospholipids that mimic the normal secondary signaling molecule, platelet-activating factor (PAF). The enzyme PAF acetylhydrolase (PAF-AH) inactivates PAF and oxidized phospholipids and constitutes an "off" switch that suppresses inflammation. Inhibition of normal PAF-AH function or inactivating mutations of the PAF-AH gene can lead to increased susceptibility to inflammatory disease. These studies have relevance to atherosclerosis and thrombosis, because inflammation is a central feature of both. (Arterioscler Thromb Vasc Biol. 2002;22:727-733.)Key Words: inflammation Ⅲ selectins Ⅲ platelet-activating factor Ⅲ chemokines Ⅲ oxidized phospholipids T his article is a summary of the Sol Sherry lecture of the Council on Arteriosclerosis, Thrombosis, and Vascular Biology, which was presented at the 73rd Scientific Sessions of the American Heart Association, New Orleans, La, November 12-15, 2000. It highlights work from our laboratory addressing the molecular basis of inflammation, particularly early events at the vascular wall. For this lecture, we have focused on our own work and have not attempted to provide a general review of this topic.In response to infection and other tissue damage, leukocytes emigrate from the bloodstream to the tissues. The adhesion of leukocytes to endothelial cells is a crucial first step in this process. When appropriately regulated, the inflammatory response is physiological and homeostatic. However, when the stimulus is spatially, temporally, or quantitatively inappropriate, adhesion and activation of leukocytes can have pathological effects (Figure 1). We have focused on the molecular changes responsible for these early steps. We have described a mechanism by which cells react to inflammatory signals to permit a spatially specific response and a high-fidelity reaction (Figure 2). Several different types of circulating cells use this same molecular mechanism."Signaling" cell/"responding" cell pairs of a number of different types are involved in inflammatory events, eg, endothelial cells and polymorphonuclear neutrophils (PMNs), endothelial cells and monocytes, and platelets and monocytes. We and others (see review 1 ) have shown that in all of these cases, the signaling cell communicates with the responding target cell in a multistep fashion. First, it tethers the target cell at the site of inflammation, and then it sends a signal to it through a molecule recognized ...

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“…Direct evidence for PAF release in stroke has been recently provided by studies demonstrating increased levels of PAF in blood from patients with ischemic stroke. 20 PAF is a lipid mediator that induces platelet aggregation, increases vascular permeability, and acts as an endothelial adhesion receptor for white blood cells. 6 Mononuclear cells may act as the primary source for PAF in response to lipopolysaccharide, 21 but PAF can be produced by many other cell types including endothelial cells, neutrophils, glial cells, and neurons.…”

Section: Discussionmentioning

confidence: 99%

Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

Sirén

Heldman

Doron

et al. 1992

Stroke

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Background and Purpose:We reported previously that stroke risk factors prepared the brain stem for the development of ischemia and hemorrhage and induced the production of tumor necrosis factor following an intrathecal injection of lipopolysaccharide, a prototypic monocyte-activating stimulus. This study evaluates whether blood or brain cells of hypertensive rats produce more proinflammatory and prothrombotic mediators than do blood or brain cells of normotensive rats.Methods: Levels of tumor necrosis factor, platelet-activating factor, 6-ketoprostaglandin F la , and thromboxane B 2 in the cerebrospinal fluid and blood of spontaneously hypertensive and normotensive Wistar-Kyoto rats were monitored before and after a challenge with lipopolysaccharide.Results: Little or no activity from these mediators was found in the cerebrospinal fluid or blood of saline-injected control animals. Intravenous administration of lipopolysaccharide (0.001, 0.1, and 1.8 nig/kg) produced dose-dependent increases in blood levels of all mediators in hypertensive rats. In normotensive rats the levels were less than in hypertensive rats and were not clearly dose-related. When lipopolysaccharide was injected intracerebroventricularly, more tumor necrosis factor was measured in the cerebrospinal fluid than in the blood, suggesting local synthesis of this cytokine. Levels of tumor necrosis factor and platelet-activating factor in the cerebrospinal fluid were higher in hypertensive than in normotensive rats. The thromboxane A 2 /prostacyclin ratio was not altered significantly between the two rat strains.Conclusions: It is suggested that the higher incidence of brain stem ischemia and hemorrhage after the intrathecal injection of lipopolysaccharide in hypertensive rats than in normotensive rats might be related to the higher levels of the two cytotoxic factors tumor necrosis factor and platelet-activating factor produced in response to such challenge.

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Increased levels of blood platelet-activating factor (PAF) and PAF-like lipids in patients with ischemic stroke

Cited by 45 publications

References 30 publications

Plasma PAF-acetylhydrolase in patients with coronary artery disease: results of a cross-sectional analysis

Plasma PAF-acetylhydrolase in patients with coronary artery disease: results of a cross-sectional analysis

Sol Sherry Lecture in Thrombosis

Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

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